CA3197961A1 - Peptide crosslinking agent and crosslinked peptide which is crosslinked using said crosslinking agent - Google Patents

Peptide crosslinking agent and crosslinked peptide which is crosslinked using said crosslinking agent

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Publication number
CA3197961A1
CA3197961A1 CA3197961A CA3197961A CA3197961A1 CA 3197961 A1 CA3197961 A1 CA 3197961A1 CA 3197961 A CA3197961 A CA 3197961A CA 3197961 A CA3197961 A CA 3197961A CA 3197961 A1 CA3197961 A1 CA 3197961A1
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Canada
Prior art keywords
peptide
protein
alkyl group
group
phenyl group
Prior art date
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Pending
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CA3197961A
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French (fr)
Inventor
Yuji Ito
Hiroshi Nakayama
Md Abdur Rafique
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Kagoshima University NUC
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Kagoshima University NUC
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Publication of CA3197961A1 publication Critical patent/CA3197961A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/16—Saturated compounds containing keto groups bound to acyclic carbon atoms containing halogen
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/10—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using coupling agents
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/16—Extraction; Separation; Purification by chromatography
    • C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2/00—Peptides of undefined number of amino acids; Derivatives thereof
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/16—Oxytocins; Vasopressins; Related peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site

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Abstract

A protein or peptide crosslinking agent which is represented by formula (I). [In the formula, A is a hydrogen atom, a C1-6 alkyl group which may be substituted with a phenyl group or a halogen atom, or a phenyl group.]

Description

ABSTRACT
A crosslinking agent for a protein or a peptide is represented by the following formula (I). In the formula, A is a hydrogen atom, a Cl to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, or a phenyl group.
NEIL
( Hal I)'----iyA

24683968.1

Claims (33)

86
1. A crosslinking agent for a protein or a peptide, represented by the following formula (I):
wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, or a phenyl group.
2. A method for producing a crosslinked protein or peptide in which at least two thiol groups in a single or separated protein(s) or peptide(s) are bound as represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, and Protein/Peptide A and Protein/Peptide B
are optionally the same or different]
comprising reacting the protein or the peptide with the crosslinking agent according to claim 1, to bind the two thiol groups via the following group:
[Chem. 3]
24683968.1 [wherein A is a hydrogen atom, a C1 to b alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group].
3. The method according to claim 2, wherein the protein or the peptide is a protein or a peptide wherein all or a part of the at least two thiol groups form a disulfide bond, and the method comprises reducing the disulfide bond to thereby generate two thiol groups.
4. A method for improving alkali resistance of a protein or a peptide, comprising binding thiol groups in the protein or the peptide to obtain a crosslinked protein or peptide by the method according to claim 2 or 3.
5. A method for producing a protein or a peptide bound to a reactive functional group which is represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional 24683968.1 group;]
comprising:
obtaining the crosslinked protein or peptide by the method according to claim 2 or 3; and reacting the crosslinked protein or peptide obtained, with NH2-L-Z (L
represents a linker and Z represents the reactive functional group), to thereby introduce a reactive functional group into a crosslinked portion of the crosslinked protein or peptide.
6. A method for producing a protein(s) or a peptide(s) bound to a reactive functional group which is represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional group;]
comprising:
reacting a crosslinked protein(s) or peptide(s) represented by the following formula:
[Chem. 6]
24683968.1 [wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, and Protein/Peptide A and Protein/Peptide B
are optionally the same or different;]
and NH2-L-Z (L represents a linker and Z represents the reactive functional group), to thereby introduce the reactive functional group to a crosslinked portion of the crosslinked protein(s) or peptide(s).
7. A method for producing a complex of a protein(s) or peptide(s) and a drug represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a Cl to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and D represents the drug;]
comprising:
obtaining a protein(s) or a peptide(s) bound to a reactive functional group by the method according to claim 5 or 6; and reacting the obtained protein(s) or peptide(s) bound to the reactive 24683968.1 functional group and the drug having another functional group reactive with the reactive functional group, to thereby bind the drug to a crosslinked portion of the crosslinked protein(s) or peptide(s).
8.
A method for producing a complex of a protein(s) or a peptide(s) and a drug represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and D represents the drug;]
comprising:
reacting a protein(s) or a peptide(s) bound to a reactive functional group which is represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a Cl to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional 24683968.1 group;]
and the drug having another functional group reactive with the reactive functional group, to thereby bind the drug to a crosslinked portion of the crosslinked protein(s) or peptide(s).
9. The method according to any one of claims 5 to 8, wherein the linker contains a moiety cleavable by a proteolytic enzyme.
10. The method according to any one of claims 2 to 9, wherein the protein or the peptide is a peptide of 5 to 50 amino acids.
11. The method according to any one of claims 2 to 10, wherein the thiol groups for crosslinking are present in a single protein or peptide.
12. The method according to claim 11, wherein the protein or peptide is an Fc-binding peptide.
13. The method according to any one of claims 2 to 10, wherein the thiol groups for crosslinking are present in separated proteins or peptides.
14. A crosslinked protein(s) or peptide(s) represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide 24683968.1 represents a protein or a peptide, and Protein/Peptide A and Protein/Peptide B
are optionally the same or different].
15. A protein(s) or a peptide(s) bound to a reactive functional group represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and Z represents the reactive functional group].
16. A complex of a protein(s) or a peptide(s) and a drug represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a Cl to 6 alkyl group, Protein/Peptide represents a protein or a peptide, Protein/Peptide A and Protein/Peptide B are optionally the same or different, L represents a linker and D represents the drug].
24683968.1
17. The protein(s) or the peptide(s) according to claim 14, the protein(s) or peptide(s) according to claim 15, or the complex according to claim 16, wherein the linker contains a moiety cleavable by a proteolytic enzyme.
18. The protein, the peptide or the complex according to any one of claims 14 to 17, wherein the protein or the peptide is a peptide of 5 to 50 amino acids.
19. The protein, the peptide or the complex according to any one of claims 14 to 18, wherein the thiol groups for crosslinking are present in a single protein or peptide.
20. The protein, the peptide or the complex according to claim 19, wherein the protein or the peptide is an Fc-binding peptide.
21. The protein, the peptide or the complex according to claim 20, wherein an amino group in a lysine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, diaminopropionic acid, an arginine residue or an amino acid at the 1-position in the Fc-binding peptide, is modified with DSG
(disuccinimidyl glutarate), DSS (disuccinimidyl suberate), DMA (dimethyl adipimidate dihydrochloride), DMP (dimethyl pimelimidate dihydrochloride), DMS (dimethyl suberimidate dihydrochloride), DTBP (dimethyl 3,3'-dithiobispropionimidate dihydrochloride), or DSP (dithiobis(succinimidyl propionic acid)).
22. The protein, the peptide or the complex according to any one of claims 14 to 18, wherein the thiol groups for crosslinking are present in separated proteins or peptides.
23. A method for producing an lgG-Fc region-containing molecule bound to a crosslinked Fc-binding peptide(s), comprising contacting an lgG-Fc region-containing 24683968.1 molecule and the protein, the peptide or the complex according to claim 20 or 21.
24. A method for producing an lgG-Fc region-containing molecule bound to a crosslinked Fc-binding peptide(s), comprising:
reacting an Fc-binding peptide bound to an lgG-Fc region-containing molecule, and the crosslinking agent according to claim 1, to bind two thiol groups in the Fc-binding peptide via the following group:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group].
25. A method for producing an lgG-Fc region-containing molecule bound to an Fc-binding peptide having a reactive functional group Z, wherein the Fc-binding peptide is represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a Cl to 6 alkyl group, L
represents a linker and Z represents the reactive functional group;]
comprising:
reacting an lgG-Fc region-containing molecule bound to a crosslinked Fc-24683968.1 binding peptide represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl groupj and NH2-L-Z (L represents a linker and Z represents the reactive functional group), to thereby introduce the reactive functional group into a crosslinked portion in the crosslinked Fc-binding peptide.
26.
A method for producing an lgG-Fc region-containing molecule bound to an Fc-binding peptide having a drug D, wherein the Fc-binding peptide is represented by the following formula:
comprising:
reacting an lgG-Fc region-containing molecule bound to an Fc-binding peptide(s) having a reactive functional group Z, wherein the Fc-binding peptide is represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a 24683968.1 phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, L
represents a linker and Z represents the reactive functional group;]
and the drug having another functional group reactive with the reactive functional group Z, to thereby bind the drug to a crosslinked portion of a crosslinked protein or peptide.
27. The method according to any one of claims 23 to 26, further comprising covalently binding the Fc-binding peptide and the lgG-Fc region-containing molecule.
28. An lgG-Fc region-containing molecule to which the protein, the peptide or the complex according to claim 20 or 21 is bound.
29. The molecule according to claim 28, wherein the Fc-binding peptide and the lgG-Fc region-containing molecule are covalently bound.
30. A carrier to which the peptide according to claim 20 or 21 is bound.
31. A method for purifying an lgG-Fc region-containing molecule, the method comprising:
contacting a liquid containing an lgG-Fc region-containing molecule, with the carrier according to claim 30;
removing a component not binding to the carrier, by washing; and eluting a component bound to the carrier, to recover the lgG-Fc region-containing molecule.
32. A method for producing a crosslinked protein or peptide in which at least two thiol groups are bound as, wherein the crosslinked protein or peptide is represented by the following formula:
24683968.1 [wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a C1 to 6 alkyl group, and Protein/Peptide represents a protein or a peptide;]
comprising:
synthesizing the protein or peptide by an Fmoc method; and using a compound represented by the following formula, instead of at least one cysteine residue, in the synthesis.
33.
A method for producing a protein or a peptide bound to a reactive functional group represented by the following formula:
[wherein A is a hydrogen atom, a C1 to 6 alkyl group optionally substituted with a phenyl group or a halogen atom, a phenyl group, or a Cl to 6 alkyl group, Protein/Peptide represents a protein or a peptide, L represents a linker, Z represents the reactive functional group and D represents a drug;]
comprising:
synthesizing the protein or peptide by an Fmoc method; and 24683968.1 using a compound represented by the following formula, instead of at least one cysteine residue, in the synthesis.
24683968.1
CA3197961A 2020-11-09 2021-10-22 Peptide crosslinking agent and crosslinked peptide which is crosslinked using said crosslinking agent Pending CA3197961A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
JP2020-186833 2020-11-09
JP2020186833 2020-11-09
JP2021-082739 2021-05-14
JP2021082739 2021-05-14
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